Preparation of cyclohexene isotopologues and stereoisotopomers from benzene.

The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine1. Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules1. Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington's disease2, was recently approved by the United States' Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial1,3,4. The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound5, improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug6,7, these processes are often unselective and the stereoisotopic purity can be difficult to measure7,8. Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.

Delta-5 elongase knockout reduces docosahexaenoic acid and lipid synthesis and increases heat sensitivity in a diatom.

Recent global marine lipidomic analysis reveals a strong relationship between ocean temperature and phytoplanktonic abundance of omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential for human nutrition and primarily sourced from phytoplankton in marine food webs. In phytoplanktonic organisms, EPA may play a major role in regulating the phase transition temperature of membranes, while the function of DHA remains unexplored. In the oleaginous diatom Phaeodactylum tricornutum, DHA is distributed mainly on extraplastidial phospholipids, which is very different from the EPA enriched in thylakoid lipids. Here, CRISPR/Cas9-mediated knockout of delta-5 elongase (ptELO5a), which encodes a delta-5 elongase (ELO5) catalyzing the elongation of EPA to synthesize DHA, led to a substantial interruption of DHA synthesis in P. tricornutum. The ptELO5a mutants showed some alterations in transcriptome and glycerolipidomes, including membrane lipids and triacylglycerols under normal temperature (22°C), and were more sensitive to elevated temperature (28°C) than wild type. We conclude that PtELO5a-mediated synthesis of small amounts of DHA has indispensable functions in regulating membrane lipids, indirectly contributing to storage lipid accumulation, and maintaining thermomorphogenesis in P. tricornutum. This study also highlights the significance of DHA synthesis and lipid composition for environmental adaptation of P. tricornutum.

Resting-state EEG dynamic functional connectivity distinguishes non-psychotic major depression, psychotic major depression and schizophrenia.

This study aims to identify dynamic patterns within the spatiotemporal feature space that are specific to nonpsychotic major depression (NPMD), psychotic major depression (PMD), and schizophrenia (SCZ). The study also evaluates the effectiveness of machine learning algorithms based on these network manifestations in differentiating individuals with NPMD, PMD, and SCZ. A total of 579 participants were recruited, including 152 patients with NPMD, 45 patients with PMD, 185 patients with SCZ, and 197 healthy controls (HCs). A dynamic functional connectivity (DFC) approach was employed to estimate the principal FC states within each diagnostic group. Incremental proportions of data (ranging from 10% to 100%) within each diagnostic group were used for variability testing. DFC metrics, such as proportion, mean duration, and transition number, were examined among the four diagnostic groups to identify disease-related neural activity patterns. These patterns were then used to train a two-layer classifier for the four groups (HC, NPMD, PMD, and SCZ). The four principal brain states (i.e., states 1,2,3, and 4) identified by the DFC approach were highly representative within and across diagnostic groups. Between-group comparisons revealed significant differences in network metrics of state 2 and state 3, within delta, theta, and gamma frequency bands, between healthy individuals and patients in each diagnostic group (p < 0.01, FDR corrected). Moreover, the identified key dynamic network metrics achieved an accuracy of 73.1 ± 2.8% in the four-way classification of HC, NPMD, PMD, and SCZ, outperforming the static functional connectivity (SFC) approach (p < 0.001). These findings suggest that the proposed DFC approach can identify dynamic network biomarkers at the single-subject level. These biomarkers have the potential to accurately differentiate individual subjects among various diagnostic groups of psychiatric disorders or healthy controls. This work may contribute to the development of a valuable EEG-based diagnostic tool with enhanced accuracy and assistive capabilities.

Profiling of the gene expression and alternative splicing landscapes of Eucalyptus grandis.

Eucalyptus is a widely planted hardwood tree species due to its fast growth, superior wood properties and adaptability. However, the post-transcriptional regulatory mechanisms controlling tissue development and stress responses in Eucalyptus remain poorly understood. In this study, we performed a comprehensive analysis of the gene expression profile and the alternative splicing (AS) landscape of E. grandis using strand-specific RNA-Seq, which encompassed 201 libraries including different organs, developmental stages, and environmental stresses. We identified 10 416 genes (33.49%) that underwent AS, and numerous differentially expressed and/or differential AS genes involved in critical biological processes, such as primary-to-secondary growth transition of stems, adventitious root formation, aging and responses to phosphorus- or boron-deficiency. Co-expression analysis of AS events and gene expression patterns highlighted the potential upstream regulatory role of AS events in multiple processes. Additionally, we highlighted the lignin biosynthetic pathway to showcase the potential regulatory functions of AS events in the KNAT3 and IRL3 genes within this pathway. Our high-quality expression atlas and AS landscape serve as valuable resources for unravelling the genetic control of woody plant development, long-term adaptation, and understanding transcriptional diversity in Eucalyptus. Researchers can conveniently access these resources through the interactive ePlant browser (https://bar.utoronto.ca/eplant_eucalyptus).

Hydride-Containing Pt-doped Cu-rich Nanoclusters: Synthesis, Structure, and Electrocatalytic Hydrogen Evolution.

A structurally precise hydride-containing Pt-doped Cu-rich nanocluster [PtH2 Cu14 {S2 P(Oi Pr)2 }6 (CCPh)6 ] (1) has been synthesized. It consists of a bicapped icosahedral Cu14 cage that encapsulates a linear PtH2 unit. Upon the addition of two equivalents of CF3 COOH to 1, two hydrido clusters are isolated. These clusters are [PtHCu11 {S2 P(Oi Pr)2 }6 (CCPh)4 ] (2), which is a vertex-missing Cu11 cuboctahedron encaging a PtH moiety, and [PtH2 Cu11 {S2 P(Oi Pr)2 }6 (CCPh)3 ] (3), a distorted 3,3,4,4,4-pentacapped trigonal prismatic Cu11 cage enclosing a PtH2 unit. The electronic structure of 2, analyzed by Density Functional Theory, is a 2e superatom. The electrocatalytic activities of 1-3 for hydrogen evolution reaction (HER) were compared. Notably, Cluster 2 exhibited an exceptionally excellent HER activity within metal nanoclusters, with an onset potential of -0.03 V (at 10 mA cm-2 ), a Tafel slope of 39 mV dec-1 , and consistent HER activity throughout 3000 cycles in 0.5 M H2 SO4 . Our study suggests that the accessible central Pt site plays a crucial role in the remarkable HER activity and may provide valuable insights for establishing correlations between catalyst structure and HER activity.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Attributing Atmospheric Phosphorus in the Himalayas: Biomass Burning vs Mineral Dust.

Atmospheric phosphorus is a vital nutrient for ecosystems whose sources and fate are still debated in the fragile Himalayan region, hindering our comprehension of its local ecological impact. This study provides novel insights into atmospheric phosphorus based on the study of total suspended particulate matter at the Qomolangma station. Contrary to the prevailing assumptions, we show that biomass burning (BB), not mineral dust, dominates total dissolved phosphorus (TDP, bioavailable) deposition in this arid region, especially during spring. While total phosphorus is mainly derived from dust (77% annually), TDP is largely affected by the transport of regional biomass-burning plumes from South Asia. During BB pollution episodes, TDP causing springtime TDP fluxes alone accounts for 43% of the annual budget. This suggests that BB outweighs dust in supplying bioavailable phosphorus, a critical nutrient, required to sustain Himalayas' ecological functions. Overall, this first-hand field evidence refines the regional and global phosphorus budget by demonstrating that BB emission, while still unrecognized, is a significant source of P, even in the remote mountains of the Himalayas. It also reveals the heterogeneity of atmospheric phosphorus deposition in that region, which will help predict changes in the impacted ecosystems as the deposition patterns vary.

Schizophrenia and risk preference: a bidirectional two-sample mendelian randomization study.

Increasing evidence shows that risk preference is associated with schizophrenia. However, the causality and direction of this association are not clear; Therefore, we used Mendelian randomization (MR) to examine the potential bidirectional relationship between risk preference and schizophrenia. Genome-wide association studies (GWAS) summary data on risk preference of 939,908 participants from the UK Biobank and 23andMe were used to identify general risk preference. Data from 320,404 subjects (76,755 cases and 243,649 controls) from The Psychiatric Genomics Consortium were used to identify schizophrenia. The weighted median (WM), the inverse variance weighted (IVW), and the Mendelian randomization-Egger (MR-Egger) methods were used for the MR analysis to estimate the causal effect and detect the directional pleiotropy. The GWAS summary data were respectively from two combined samples, containing 939,908 and 320,404 subjects of European ancestry. Mendelian randomization evidence suggested that risk preference was associated with increased onset of schizophrenia (OR = 2.84, 95CI%: 1.77-4.56, P = 1.58*10 - 5) and that schizophrenia was also associated with raised risk preference (OR = 1.11, 95CI%: 1.07-1.15, P = 7.98*10 - 8). With the use of large-scale GWAS data, robust evidence suggests an interaction between risk preference and schizophrenia. This also indicates that early identification of and intervention for increased risk preference may improve the prognosis of schizophrenia.

Brain structural alterations associated with impulsiveness in male violent patients with schizophrenia.

BACKGROUND: Violence in schizophrenia (SCZ) is a phenomenon associated with neurobiological factors. However, the neural mechanisms of violence in patients with SCZ are not yet sufficiently understood. Thus, this study aimed to explore the structural changes associated with the high risk of violence and its association with impulsiveness in patients with SCZ to reveal the possible neurobiological basis. METHOD: The voxel-based morphometry approach and whole-brain analyses were used to measure the alteration of gray matter volume (GMV) for 45 schizophrenia patients with violence (VSC), 45 schizophrenia patients without violence (NSC), and 53 healthy controls (HC). Correlation analyses were used to examine the association of impulsiveness and brain regions associated with violence. RESULTS: The results demonstrated reduced GMV in the right insula within the VSC group compared with the NSC group, and decreased GMV in the right temporal pole and left orbital part of superior frontal gyrus only in the VSC group compared to the HC group. Spearman correlation analyses further revealed a positive correlation between impulsiveness and GMV of the left superior temporal gyrus, bilateral insula and left medial orbital part of the superior frontal gyrus in the VSC group. CONCLUSION: Our findings have provided further evidence for structural alterations in patients with SCZ who had engaged in severe violence, as well as the relationship between the specific brain alterations and impulsiveness. This work provides neural biomarkers and improves our insight into the neural underpinnings of violence in patients with SCZ.

Comparison of Lower and Upper Extremity Arteriovenous Graft: A Retrospective Clinical Analysis with 5-Year Follow-Up.

BACKGROUND: For patients in whom an upper extremity (UE) vascular access cannot be established, the lower extremity (LE) arteriovenous graft (AVG) could be selected. However, the application of LE AVG is limited owing to its high infection rate, uncertain patency time, and technical difficulties. This study aimed to compare the long-term patency rates and the incidence of vascular access complications of AVG in the LE and UE to provide a reference for the applications of AVG, especially in the LEs. METHODS: This was a retrospective analysis of patients who successfully underwent LE or UE AVG placement from March 2016 to October 2021. Patient characteristics were collected and compared using parameter or nonparameter tests according to data type. Postoperative patency was evaluated using Kaplan-Meier test. Postoperative complication incidence density and intergroup comparison were estimated using the Poisson distribution. RESULTS: Twenty-two patients with LE AVG and 120 patients with UE AVG were included. The 1-year primary patency rate was 67.4% (±11.0% standard error [SE]) in the LE group and 30.1% (±4.5% SE) in the UE group (P = 0.031). The assisted primary patency rate at postoperative months 12, 24, and 36 was respectively 78.6% (±9.6% SE), 65.5% (±14.4% SE), and 49.1% (±17.8% SE) in the LE group and 63.3% (±4.6% SE), 47.5% (±5.4% SE), and 30.4% (±6.1% SE) in the UE group (P = 0.137). The secondary patency rate at postoperative months 12, 24, and 36 remains 95.5% (±4.4% SE) in the LE group and 89.3% (±2.9% SE), 83.7% (±3.9% SE), and 73.0% (±6.2% SE), respectively, in the UE group (P = 0.200). Postoperative complications included stenosis, occlusion/thrombosis, infection, steal syndrome, pseudoaneurysm, severe postoperative serum swelling, and AVG exposure. The total incidence rates of postoperative complications were 0.87 (95% confidence interval [CI] 0.59-1.23) versus 1.61 (95% CI 1.45-1.79) (P = 0.001) cases/person-year, the incidence rates of stenosis were 0.45 (95% CI 0.26-0.73) versus 0.92 (95% CI 0.80-1.06) (P = 0.005) cases/person-year and the incidence rates of occlusion/thrombosis were 0.34 (95% CI 0.17-0.59) versus 0.62 (95% CI 0.52-0.74) cases/person-year in the LE group compared to those in the UE group (P = 0.041). CONCLUSIONS: LE AVG had higher primary patency rate and lower postoperative complication incidence than UE AVG. With the development of interventional technology, both LE AVG and UE AVG exhibited high secondary patency rates. LE AVG can be a reliable and long-term alternative for appropriately selected patients with unusable UE vessels.

The impact of workplace violence on job burnout among Chinese correctional officers: the chain mediating effects of stress and insomnia.

BACKGROUND: The risk of workplace violence and job burnout among Chinese correctional officers is high. Stress and insomnia may influence the relationship between workplace violence and job burnout; however, this influence has been rarely studied. This study aimed to explore the effect of workplace violence on job burnout among Chinese correctional officers and to assess the contribution of stress and insomnia to this effect. METHODS: In this study, the workplace violence scale, the Assens insomnia scale, the 21-item Depression Anxiety Stress Scale, and the Maslach Burnout Inventory-General Survey scale were used to assess the workplace violence, insomnia, stress, and job burnout experienced by the 472 correctional officers, respectively. RESULTS: The results showed that (1) workplace violence was significantly and positively predictive of job burnout, (2) workplace violence affected job burnout through the mediation of stress, (3) workplace violence affected job burnout through the mediation of insomnia, and (4) stress and insomnia played fully interlocking mediating roles in the effect of workplace violence on job burnout. CONCLUSION: Stress and insomnia may play a full mediating role in the relationship between workplace violence and job burnout. This suggested that correctional officers may take measures to reduce stress and improve insomnia, thereby reducing their job burnout. Further research may focus on the development of effective interventions to reduce stress and improve insomnia among correctional officers.

Relationship between work-family conflict and anxiety/depression among Chinese correctional officers: a moderated mediation model of burnout and resilience.

BACKGROUND: Correctional officers tend to have high levels of work-family conflict (WFC). WFC has been found associated with various forms of psychological distress and to affect the overall well-being of correctional officers. Burnout and resilience may affect the relationship between WFC and psychological distress, however, this association still remains unclear. This study aimed to examine the mediating effect of burnout on the relationship between WFC and anxiety/depression and the moderating role of resilience, within the context of correctional officers. METHODS: A cross-sectional online survey was conducted in China from October 2021 to January 2022. WFC, burnout, resilience, anxiety, and depression were evaluated using the Work-Family Conflict Scale (WFCS), Maslach Burnout Inventory-General Survey (MBI-GS), 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the Depression Anxiety Stress Scale (DASS). Mediation and moderation models were then tested using the PROCESS macro in SPSS, with burnout being a mediator and resilience playing a moderating role in the relationship between WFC and anxiety/depression. RESULTS: A total of 472 correctional officers were included. Burnout was found to mediate the relationship between WFC and anxiety (b = 0.14, 95%CI [0.10, 0.19]) and the relationship between WFC and depression (b = 0.23, 95%CI [0.18, 0.28]). Additionally, resilience played a moderating role in the direct effect of WFC on anxiety (b = - 0.02, p < 0.01) and the first half of the indirect effect of WFC on anxiety (b = - 0.007, p < 0.05). Furthermore, resilience was also found to moderate the first half of the indirect effect of WFC on depression (b = - 0.02, p < 0.01), but not the direct effect of WFC on depression (b = - 0.005, p > 0.05). CONCLUSION: The findings of the present study may improve our understanding by elucidating the fundamental mechanisms of the connection between WFC and psychological distress among correctional officers. The results have significant implications for policymakers and individuals, as they suggest that diverse interventions may help promote the mental well-being of correctional officers.

Differences in the depression and burnout networks between doctors and nurses: evidence from a network analysis.

BACKGROUND: Previous studies have demonstrated a strong association between depression and job burnout among healthcare professionals, but the results have been inconsistent, and there is a lack of in-depth exploration of such a relationship among different healthcare professions. The present study aims to investigate the interrelationships between depression and burnout among Chinese healthcare professionals and whether there are differences in the networks of these symptoms between doctors and nurses. METHODS: The Maslach Burnout Inventory-General Survey and the 2-item Patient Health Questionnaire were employed to assess job burnout and depression among 3,684 healthcare professionals. The translation has been refined to ensure accuracy and academic suitability. Subsequently, network analysis was conducted on 2,244 participants with a higher level of job burnout to identify core symptoms and explore the associations between job burnout and depression. RESULTS: The present study showed a network association between lack of interest and pleasure in things and being exhausted from work, excessive tiredness facing work, tendency to collapse at work, and lack of passion for work than before among healthcare professionals, as well as a notable difference in the network association between lack of interest and pleasure in things and lack of passion for work than before between nurses and doctors. CONCLUSIONS: The depression-burnout network structures differ between doctors and nurses, highlighting the need for targeted intervention measures for both groups.

Neutron Instruments for Research in Coordination Chemistry.

Neutron diffraction and spectroscopy offer unique insight into structures and properties of solids and molecular materials. All neutron instruments located at the various neutron sources are distinct, even if their designs are based on similar principles, and thus, they are usually less familiar to the community than commercial X-ray diffractometers and optical spectrometers. Major neutron instruments in the USA, which are open to scientists around the world, and examples of their use in coordination chemistry research are presented here, along with a list of similar instruments at main neutron facilities in other countries. The reader may easily and quickly find from this minireview an appropriate neutron instrument for research. The instruments include single-crystal and powder diffractometers to determine structures, inelastic neutron scattering (INS) spectrometers to probe magnetic and vibrational excitations, and quasielastic neutron scattering (QENS) spectrometers to study molecular dynamics such as methyl rotation on ligands. Key and unique features of the diffraction and neutron spectroscopy that are relevant to inorganic chemistry are reviewed.

Steroid hormone ecdysone deficiency stimulates preparation for photoperiodic reproductive diapause.

Diapause, a programmed developmental arrest primarily induced by seasonal environmental changes, is very common in the animal kingdom, and found in vertebrates and invertebrates alike. Diapause provides an adaptive advantage to animals, as it increases the odds of surviving adverse conditions. In insects, individuals perceive photoperiodic cues and modify endocrine signaling to direct reproductive diapause traits, such as ovary arrest and increased fat accumulation. However, it remains unclear as to which endocrine factors are involved in this process and how they regulate the onset of reproductive diapause. Here, we found that the long day-mediated drop in the concentration of the steroid hormone ecdysone is essential for the preparation of photoperiodic reproductive diapause in Colaphellus bowringi, an economically important cabbage beetle. The diapause-inducing long-day condition reduced the expression of ecdysone biosynthetic genes, explaining the drop in the titer of 20-hydroxyecdysone (20E, the active form of ecdysone) in female adults. Application of exogenous 20E induced vitellogenesis and ovarian development but reduced fat accumulation in the diapause-destined females. Knocking down the ecdysone receptor (EcR) in females destined for reproduction blocked reproductive development and induced diapause traits. RNA-seq and hormone measurements indicated that 20E stimulates the production of juvenile hormone (JH), a key endocrine factor in reproductive diapause. To verify this, we depleted three ecdysone biosynthetic enzymes via RNAi, which confirmed that 20E is critical for JH biosynthesis and reproductive diapause. Importantly, impairing Met function, a component of the JH intracellular receptor, partially blocked the 20E-regulated reproductive diapause preparation, indicating that 20E regulates reproductive diapause in both JH-dependent and -independent manners. Finally, we found that 20E deficiency decreased ecdysis-triggering hormone signaling and reduced JH production, thereby inducing diapause. Together, these results suggest that 20E signaling is a pivotal regulator that coordinates reproductive plasticity in response to environmental inputs.

XGBoost in the Prediction of 28-Day Mortality in Critical Elderly Patients with Hip Fracture: A MIMIC-IV Cohort Study.

Background: The impact of hip fracture on older adults is significant, including increased mortality, reduced activity levels and abilities and reduced quality of life。 Hip fractures often occur in the elderly and increase the risk of death. The purpose of this study is to analyze the risk factors associated with 28-day mortality in elderly patients with severe hip fractures using two models, XG Boost and multivariate logistic regression, and to compare the predictive value of the two models. Methods: MIMIC database is a powerful tool to provide clinical data to clinical researchers. The database was established in 2003 with funding from the National Institutes of Health by the Computational Physiology Laboratory at the Massachusetts Institute of Technology, Beth Israel Deaconess Medical Center (BIDMC) at Harvard Medical School, and Philips Medical. Patients with severe hip fractures in the elderly were included based on the MIMIC-IV database and were divided into a death group and a survival group based on the death 28 days after admission to the ICU. Baseline data differences between the two groups of patients were compared, and risk factors associated with 28-day mortality in severe elderly patients with hip fractures were analyzed using XG Boost and multivariate logistic regression models, respectively. The predictive power of the two models was compared using receiver operation characteristics curves. Results: 287 elderly patients with severe hip fractures were included, including 43 cases (15.0%) in the death group and 244 cases (85.0%) in the survival group. Logistic regression analysis showed that advanced age, male, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), high sepsis-related organ failure (SOFA) score, high heart rate, high white blood cell count, high creatinine, high mean arterial pressure, and high hemoglobin levels were associated with 28-day mortality after admission to the ICU, while the higher the mean arterial pressure and the hemoglobin level, the lower the risk of death. Although the rate of using mechanical ventilation and receiving blood transfusion in the death group was higher than that in the survival group, neither of them reached statistical significance. The XG Boost model shows that the top 5 factors associated with 28-day mortality are Sequential organ failure score (SOFA) score (31 points), chronic heart failure (20 points), chronic structural pulmonary disease (18 points), age (17 points), and male (15 points). The higher the mean arterial pressure and the hemoglobin level, the lower the risk of death. The area under the ROC curve predicted by the multivariate logistic regression model for mortality risk was 0.729 (95% CI: 0.701-0.783), and the Jordan index was 0.412. The area under the ROC curve predicted by the XG Boost model for mortality risk was 0.804 (95% CI: 0.720-0.837), and the Jordan index was 0.492. Conclusion: The ability of the XG Boost model to predict the 28-day mortality risk in elderly patients with severe hip fractures is better than the multivariate logistic regression model, which will help healthcare professionals provide more support for elderly patients with hip fracture.

Electroacupuncture Promotes Skeletal Muscle Myogenic Differentiation and Protein Synthesis by Reducing Let-7c-5p Levels.

Objective: Acupuncture with low-frequency electrical stimulation (Acu-LFES) can attenuate muscle atrophy. Previous studies have found that Acu-LFES reduces the let-7 family in serum exosomes. This study explored the effects of let-7c-5p in chronic kidney disease (CKD) muscle atrophy. Methods: A total of 24 mice were randomly divided into control group, Acu-LFES group, CKD group, and CKD/Acu-LFES group (n = 6/group). The 5/6 nephrectomy was performed to establish the CKD model in mice. After 20 weeks, the Acu-LFES group and CKD/Acu-LFES group were treated with electroacupuncture at the "Zu San Li" and "Yang Ling Quan" bilaterally points for 15 minutes once. Surface sensing of translation (SUnSET), Reverse Transcription-quantitative PCR(RT-qPCR), immunofluorescence staining, and Western blot were performed to examine each group's state of protein production and myogenic differentiation. we knocked down or exogenously expressed let-7c-5p in C2C12 myoblast, RT-qPCR, and Western blot were performed to examine protein synthesis and myogenic differentiation. Results: The protein expressions of MyoD and Myogenin (MyoG) were decreased in the CKD group (P = .029 and P = .026) concomitant with a decrease in the muscle fiber cross-sectional area. Acu-LFES prevented muscle atrophy in CKD mice. The protein expressions of MyoD and MyoG were increased in the CKD/Acu-LFES group (P = .006 and P = .001). In muscle of CKD mice, IGF1, IGF1R, IRS1, phosphorylated mTOR and P70S6K proteins were decreased compared with control muscle (P = .001, P = .007, P < .001, P < .001 and P < .001), whereas atrogin-1/MAFbx and MuRF1 were dramatically increased (P < .001). Acu-LFES reversed these phenomena, indicating IGF1/mTOR signaling pathway was induced to promote muscle protein synthesis and myogenic differentiation. Meanwhile, Acu-LFES caused a decrease of let-7c-5p in skeletal muscle of CKD mice (P = .034). Inhibiting let-7c-5p promoted C2C12 myogenic differentiation (P = .002 and P = .001) and increased IGF1, IGF1R, IRS1 levels while upregulating mTOR and P70S6K phosphorylation (P < .001, P = .002, P = .009, P < .001 and P = .007). It is interesting to observe that the abundance of atrogin-1/MAFbx and MuRF-1 was unaffected by let-7c-5p (P > .05). Conclusions: Acu-LFES-reduced expression of let-7c-5p can ameliorate CKD-induced skeletal muscle atrophy by upregulating the IGF1/mTOR signaling pathway, which enhances skeletal muscle protein synthesis and myogenic differentiation. Let-7c-5p may be a potential regulator for the treatment of muscle atrophy.

Combined Mindfulness-Based Stress Reduction and Exercise Intervention for Improving Psychological Well-Being in Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: This study aims to assess the clinical effectiveness of combining mindfulness-based stress reduction (MBSR) with exercise intervention in improving anxiety, depression, sleep quality and mood regulation in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 60 patients with NSCLC who had not received surgical treatment were selected using convenience sampling and divided into an intervention group and control group, with 30 patients in each group. The control group received conventional psychological nursing care, whereas the intervention group received a combination of MBwSR and exercise therapy. Before the intervention, a questionnaire was completed to collect the basic data of the two groups. Further questionnaires were administered at 6 and 8 weeks after treatment to assess anxiety, depression, sleep quality and other items included in the five-item Brief Symptom Rating Scale (BSRS-5). RESULTS: No significant differences between the intervention and control groups were identified in terms of personal and clinical characteristics (p > 0.05). No significant differences were determined in the BSRS-5, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) or Pittsburgh Sleep Quality Index (PSQI) scores between the intervention and control groups before the intervention. However, 6 and 8 weeks after the intervention, scores were significantly lower in both groups (p < 0.001). Significant differences in the BSRS-5, SAS, SDS and PSQI scores were identified between the two groups at different time points (p < 0.001). CONCLUSION: The combination of MBSR and exercise intervention demonstrated improvements in anxiety, depression, sleep quality and BSRS-5 scores in patients with NSCLC.

A comparative study of the use of digital technology in the anterior smile experience.

OBJECTIVES: this study aims to compare the clinical outcomes of traditional and digital crown extension guides in the aesthetic restoration of anterior teeth. Additionally, the study will analyze the differences in the results of various digital crown extension guides in anterior aesthetic restorations. METHODS: Sixty-two patients who required aesthetic restoration of their anterior teeth were selected for this study. The patients had a total of 230 anterior teeth and were randomly divided into three groups: a control group of 22 cases who received diagnostic wax-up with pressure film, an experimental group 1 of 20 cases who received 3D printed digital models with pressure film, and an experimental group 2 of 20 patients who received digital dual-positioning guides. The control group had a total of 84 anterior teeth, experimental group 1 had 72 anterior teeth, and experimental group 2 had 74 anterior teeth. The study compared three methods for fabricating crown extension guides: the control group used the diagnostic wax-up plus compression film method, while experimental group 1 used compression film on 3D printed models and experimental group 2 used 3D printed digital dual-positioning crown extension guides. After the crown lengthening surgery, the control group patients wore DMG resin temporary crown material for gingival contouring, while the experimental group patients wore 3D printed resin temporary crowns for the same purpose. The patients were followed up in the outpatient clinic after wearing temporary crowns for 1 month, 3 months, and 6 months, respectively. The clinical results were evaluated in terms of marginal fit, red aesthetic index, and white aesthetic index. RESULTS: Based on the statistical analysis, the experimental group required significantly fewer follow-up visits and less time for guide design and fabrication compared to the control group. Additionally, the surgical time for the experimental group was significantly shorter than that of the control group. During the postoperative period between the 1st and 3rd month, the PES index scores for the marginal gingival level, proximal, and distal mesiodistal gingival papillae of the experimental group showed a trend of superiority over those of the control group. By the 6th month, the marginal gingival level exhibited a significant difference between the experimental and control groups. The experimental group demonstrated superior results to the control group in terms of shape, contour, and volume of the teeth, color, surface texture, and transparency of the restorations, and features during the 1st and 3rd postoperative months. In the 6th month, the comparative results indicated that the experimental group continued to exhibit superior outcomes to the control group in terms of the shape, color, surface texture, and transparency of the restorations, as well as the characteristics of the teeth. Additionally, the experimental group demonstrated significantly fewer gingival alterations than the control group at 1 month, 3 months, and 6 months post-procedure, with this difference being statistically significant. Furthermore, the combination of 3D printing technology and restorative techniques was utilized, resulting in consistent patient satisfaction. CONCLUSION: Digitalisation plays an important role in anterior aesthetic restorations. The use of digital technology to manage the entire process of anterior cosmetic restorations can improve restorative results, reduce the number of follow-up appointments, shorten consultation time, and achieve better patient satisfaction.

Mechanistic Study of the Hydride Migration-Induced Reversible Isomerization in Au22(SR)15H Isomers.

Unraveling the evolution mechanism of metal nanoclusters is of great importance in understanding the formation and evolution of metallic condensed matters. In this work, the specific evolution process between a pair of gold nanocluster (Au NC) isomers is completely revealed by introducing hydride ligands to simplify the research system. A hydride-containing Au NC, Au22(SR)15H, was synthesized by kinetic control, and the positions of the hydrides were then confirmed by combining X-ray diffraction, neutron diffraction, and DFT calculations. Importantly, a reversible structural isomerization was found to occur on this Au22(SR)15H. By combining the crystal structures and theoretical calculations, the focus was placed on the hydride-binding site, and a [Au-H] migration mechanism of this isomerization process is clearly shown. Furthermore, this [Au-H] migration mechanism is confirmed by the subsequent capture and structural determination of theoretically predicted intermediates. This work provides insight into the dynamic behavior of hydride ligands in nanoclusters and a strategy to study the evolution mechanism of nanoclusters by taking the hydride ligand as the breakthrough point.